Requiring Renal Replacement Therapy Research Articles

Acute Kidney Injury and Sepsis after Cardiac Surgery: The Roles of Tissue Inhibitor Metalloproteinase-2, Insulin-like Growth Factor Binding Protein-7, and Mid-Regional Pro-Adrenomedullin.

Identifying a panel of markers detecting kidney injury before the glomerular filtration rate reduction is a challenge to improving the diagnosis and management of acute kidney injury (AKI) in septic patients. This study evaluated the roles of tissue inhibitor metal proteinase-2, insulin growth factor binding protein-7 (TIMP2*IGFBP7), and mid-regional pro-adrenomedullin (MR-proADM) in patients with AKI. This study was prospectively conducted in an intensive care unit (ICU) enrolling 230 patients who underwent cardiac surgery. Biomarkers were evaluated before and after 4 h of the cardiac surgery. Whereas urine and creatinine alterations appeared at 23.2 (12.7-36.5) hours after cardiac surgery, urinary TIMP2*IGBP7 levels were higher at 4 h in AKI patients (1.1 ± 0.4 mg/L vs. 0.08 ± 0.02 mg/L; p < 0.001). Its concentration > 2 mg/L increases AKI risk within the following 24 h, clearly identifying the population at high risk of renal replacement therapy (RRT). In patients with sepsis, MR-proADM levels were 2.3 nmol/L (0.7-7.8 nmol/L), with the highest values observed in septic shock patients (5.6 nmol/L (3.2-18 nmol/L)) and a better diagnostic profile than procalcitonin and C-reactive protein to identify septic patients. MR-proADM values > 5.1 nmol/L and urine TIMP2*IGBP7 levels > 2 mg/L showed a significantly faster progression to RRT, with a mean follow-up time of 1.1 days. TIMP2*IGBP7 and MR-proADM precociously diagnose AKI in septic patients after cardiac surgery, giving prognostic information for RRT requirement.

One-Year Outcomes of Patients Requiring Tracheostomy Placement Due to Severe Acute Respiratory Syndrome Coronavirus 2 Infection.

What are the characteristics of patients who develop the need for tracheostomy due to SARS-CoV-2 with acute respiratory distress syndrome (ARDS)? What is their 90-day and 1-year survival and are there any identifiable risk factors for mortality and ventilator dependency? Retrospective, follow-up cohort study of adult patients with COVID-19 infection and ARDS who required tracheostomy placement in a large healthcare system. One hundred sixty-four consecutive patients with SARS-CoV-2 admitted to ICUs for ARDS who required tracheostomy placement between March 2020 and March 2021 were identified. One hundred nine (66.5%) were male. Average age was 63.5 years. The most common comorbidities were obesity, hypertension, diabetes mellitus, congestive heart failure, chronic kidney disease, chronic obstructive pulmonary disease (COPD), atrial fibrillation, and asthma. The most common complications during hospitalization were delirium, secondary infections, acute kidney injury, pneumothorax, and venous thromboembolism. Ninety-day and 1-year mortality were 29.9% and 44.5%, respectively. Ninety-six patients (58.5%) were liberated from the ventilator, and 84 (51.2%) had the tracheostomy tube decannulated. Asthma, COPD, atrial fibrillation, and renal replacement therapy requirement in the ICU correlated with increased risk of ventilator dependency. Among survivors at 1 year, 71 patients (43.3%) were residing at home and 20 patients (12.2%) remained in a skilled nursing facility. COVID-19 has resulted in a significant burden of acute critical illness and acute respiratory failure with the need for tracheostomy. A significant percentage of patients with SARS-CoV-2 requiring tracheostomy were alive and at home 1 year after tracheostomy placement. Long-term care support, including tracheostomy, beyond 90 days appears to be beneficial in this patient population and warrants further investigation.

Practical considerations for individualizing drug dosing in critically ill adults receiving renal replacement therapy.

Critically ill patients with sepsis admitted to the intensive care unit (ICU) often present with or develop renal dysfunction requiring renal replacement therapy (RRT) in addition to antimicrobial therapy. While early and appropriate antimicrobials for sepsis have been associated with an increased probability of survival, adequate dosing is also required in these patients. Adequate dosing of antimicrobials refers to dosing strategies that achieve serum drug levels at the site of infection that are able to provide a microbiological and/or clinical response while avoiding toxicity from excessive antibiotic exposure. Therapeutic drug monitoring (TDM) is the recommended strategy to achieve this goal, however, TDM is not routinely available in all ICUs and for all antimicrobials. In the absence of TDM, clinicians are therefore required to make dosing decisions based on the clinical condition of the patient, the causative organism, the characteristics of RRT, and an understanding of the physicochemical properties of the antimicrobial. Pharmacokinetics (PK) of antimicrobials can be highly variable between critically ill patients and also within the same patient over the course of their ICU stay. The initiation of RRT, which can be in the form of intermittent hemodialysis, continuous, or prolonged intermittent therapy, further complicates the predictability of drug disposition. This variability highlights the need for individualized dosing. This review highlights the practical considerations for the clinician for antimicrobial dosing in critically ill patients receiving RRT.

Clinical Profile of End Stage Renal Disease Patients Undergoing Hemodialysis in a Tertiary Care Hospital of Nepal

BACKGROUND Maintenance hemodialysis is a popular treatment modality of renal replacement therapy for end stage renal disease patients. The clinical profile of end-stage renal disease (ESRD) and dialysis in Mid Western Nepal are scarce. This study aimed to study the clinical profile of ESRD patients undergoing hemodialysis at the tertiary care Hospital.&#x0D; METHODS This study was a single center based cross sectional observational study carried out over a period from 15th December 2022 to 15th February 2023 in Department of Medicine. A total of 40 patients undergoing maintenance hemodialysis were enrolled in the study. Data about Socio demographic profiles , clinical data, duration of chronic kidney disease (CKD), major comorbidity, the presumed etiology of ESRD, duration of haemodialysis, laboratory parameters including Renal function tests etc were entered in MS Excel and analyzed through SPSS 21.&#x0D; RESULTS A total of 40 patients were enrolled in the study. Males were 25(62.5%) and females were 15(37.5%). The mean age of the patient was 45.75±15.2 years. The most common cause of end stage renal disease and reasons for admission were hypertension nephropathy 36(90%) and Type 2 diabetes mellitus 9(22.5%) respectively. Anemia was the most common hematological findings in ESRD patients (&gt;90%) followed by hypocalcemia in 65%.&#x0D; CONCLUSIONS Hypertensive nephropathy was the commonest cause for CKD followed by diabetic nephropathy and glomerulonephritis. Early detection and effective management of these illnesses can delay the onset, progression of CKD to end stage and subsequent morbidity and the requirement of renal replacement therapy.

Comparison of the clinical characteristics and clinical outcomes of culture-positive septic shock and culture-negative septic shock among pediatric patients.

Among pediatric patients with septic shock, culture-negative septic shock (CNSS) is common but there have been limited data on its clinical characteristics and prognosis. We compared the clinical characteristics and clinical outcomes between culture-positive septic shock (CPSS) and CNSS in pediatric patients. Retrospective single-center study. Pediatric intensive care unit (PICU) of a tertiary referral hospital. All pediatric patients who were admitted to the PICU due to septic shock between January 2010 and November 2021, except for those with fungal or viral infections and those who expired on the day of admittance to the PICU. The primary outcome was 30-day mortality and in-hospital mortality. None. A total of 294 patients (CPSS group, n = 185 [62.9%]; CNSS group, n = 109 [37.1%]) were included. The rates of 30-day mortality and in-hospital mortality (30-day mortality 22.7% vs 22%, in-hospital mortality 29.7% vs 25.7%) were not significantly different between the CPSS group and the CNSS group. The two groups showed comparable results in clinical outcomes such as the requirement for mechanical ventilator and renal replacement therapy, PICU stay duration, and the duration of MV and vasopressor/inotrope support. Among the CPSS group, 98 (53%) patients who were infected with multi-drug resistance (MDR) bacteria had significantly higher rates of 30-day mortality and in-hospital mortality than those infected with non-MDR bacteria. Among pediatric patients, the CPSS group and CNSS group did not show significant differences in clinical features and mortality. Among the CPSS group, those with MDR bacteria had poorer prognosis.

Sepsis-associated acute kidney injury in the intensive care unit: incidence, patient characteristics, timing, trajectory, treatment, and associated outcomes. A multicenter, observational study

PurposeThe Acute Disease Quality Initiative (ADQI) Workgroup recently released a consensus definition of sepsis-associated acute kidney injury (SA-AKI), combining Sepsis-3 and Kidney Disease Improving Global Outcomes (KDIGO) AKI criteria. This study aims to describe the epidemiology of SA-AKI.MethodsThis is a retrospective cohort study carried out in 12 intensive care units (ICUs) from 2015 to 2021. We studied the incidence, patient characteristics, timing, trajectory, treatment, and associated outcomes of SA-AKI based on the ADQI definition.ResultsOut of 84,528 admissions, 13,451 met the SA-AKI criteria with its incidence peaking at 18% in 2021. SA-AKI patients were typically admitted from home via the emergency department (ED) with a median time to SA-AKI diagnosis of 1 day (interquartile range (IQR) 1–1) from ICU admission. At diagnosis, most SA-AKI patients (54%) had a stage 1 AKI, mostly due to the low urinary output (UO) criterion only (65%). Compared to diagnosis by creatinine alone, or by both UO and creatinine criteria, patients diagnosed by UO alone had lower renal replacement therapy (RRT) requirements (2.8% vs 18% vs 50%; p < 0.001), which was consistent across all stages of AKI. SA-AKI hospital mortality was 18% and SA-AKI was independently associated with increased mortality. In SA-AKI, diagnosis by low UO only, compared to creatinine alone or to both UO and creatinine criteria, carried an odds ratio of 0.34 (95% confidence interval (CI) 0.32–0.36) for mortality.ConclusionSA-AKI occurs in 1 in 6 ICU patients, is diagnosed on day 1 and carries significant morbidity and mortality risk with patients mostly admitted from home via the ED. However, most SA-AKI is stage 1 and mostly due to low UO, which carries much lower risk than diagnosis by other criteria.

Sonidegib induced rhabdomyolysis in kidney transplant patient: a case report

Kidney transplant recipients (KTR) have a higher risk of developing malignancies compared to the general population, due to the immunosuppressive regimens which can promote the oncogenesis process. The incidence of de novo non-melanoma skin cancer (NMSC) in KTR is greater than in the general population. Basal cell carcinoma (BCC) represents one of the most frequent malignancies in KTR. Sonidegib is a Hedgehog signaling pathway inhibitor approved for the treatment of locally advanced basal-cell carcinoma (LABCC) that following surgery or radiation therapy, or is given to those candidates who are not eligible to surgery or radiation therapy. This paper reports the case of a kidney transplant patient, who developed severe acute kidney injury (AKI) due to rhabdomyolysis (RML) induced by sonidegib therapy which required renal replacement therapy (RRT).

Risk Factors and Outcome of Acute Kidney Injury in Critical COVID-19 patients in Karachi, Pakistan: A Single center, Retrospective study

Introduction: The severe acute respiratory syndrome coronavirus2 (SARS-CoV2) is a novel beta-coronaviridae family and its effects on the kidneys have been reported which included the increased requirement of renal replacement therapy during the Covid-19 pandemic. Our study is,thus, designed to determine the risk factors of AKI in critically ill patients with covid-19 and their outcomes&#x0D; Method and Material: It is a retrospective observational study of COVID-19 patients admitted in SIDH&amp;RC(specialized facility center for COVID-19) from July 2020 to July 2021. The patients were divided into two groups; one with confirmed critical COVID-19 and had AKI during hospital stay and the other group who have confirmed critical COVID-19 and did not had AKI during hospital stay.&#x0D; Results: Total 232 patients included in this study who were critical at the time of admission in which 92(39.65%) of the patients had AKI during hospital stay. Most of the patients who had AKI were male 55(59.8%). We found that in this population mortality was not significant in critical COVID-19 patients with AKI. However, patients with AKI had worst survival distribution compared to non-AKI patients (p&lt;0.05). Patients with AKI required mechanical ventilation compared to non-AKI patients (70.7% vs 50.7%, p&lt;0.05) along with significant chances of occurrence of complications as superimposed bacterial infections (78.3% vs 52.9%, p&lt;0.05), NSTEMI (33.7% vs 13.6%, p&lt;0.05), septic shock (66.3% vs 38.6%, p&lt;0.05) and progression to severe ARDS (78.3% vs 60.7%, p&lt;0.05). &#x0D; Conclusion: We found that patients with AKI had a worst survival distribution than non AKI in Critical COVID-19 patients

#3153 HEMOPERFUSION WITH CYTOSORB AND RENAL REPLACEMENT THERAPY IN PATIENTS WITH ACUTE KIDNEY INJURY IN THE INTENSIVE CARE UNIT

Abstract Background and Aims Severe acute kidney injury (AKI) requiring renal replacement therapy (RRT) is a serious clinical disorder in the intensive care unit (ICU), occurring in a substantial proportion of critically ill patients. The aim of our single centre retrospective observational study was to analyse the outcomes of patients admitted to a non-surgical ICU and treated with RRT and with/without continuous hemoperfusion with Cytosorb. Method One hundred critically ill patients (mean age, 64.3 years; 69 men) admitted to the ICU and requiring RRT for AKI were analysed. Patient demographics, concomitant diseases, type of RRT, and survival were obtained from the medical record. APACHE II and Sofa Scores on admission were calculated. 30-day mortality was assessed using Kaplan-Meyer or Cox proportional hazards models. Results Reasons for ICU admission were acute respiratory failure (39%), cardiopulmonary resuscitation (14%), shock (13%), acute coronary syndrome (9%), sepsis (3%), acute pancreatitis (3%), and other (19%). Prior comorbidities were hypertension (70%), diabetes (43%), heart failure (32%), chronic kidney disease (CKD) (30%), coronary artery disease (CAD) (27%), chronic obstructive pulmonary disease (COPD) (15%), malignancies (12%). Eighty-six patients were treated with continuous RRT (CRRT) and 14 with intermittent hemodialysis (IHD). Twenty-four (24%) of patients treated with CRRT were also treated with hemoperfusion with Cytosorb. Using an independent-samples T test, we compared the two groups of patients with respect to the use of Cytosorb (Table 1). 30-day mortality was 82% in all patients and 87.5% in patients treated with CRRT and Cytosorb. Among concomitant diseases, only patients with previous heart failure had worse survival (p = 0.032), previous CKD, CAD, COPD, malignancy had no statistically significant impact. We found no statistically significant differences in 30-day mortality between patients treated with CRRT+Cytosorb and patients treated with CRRT or IHD alone. Multivariate Cox proportional hazard regression showed that of all the variables in the statistical model (age, sex, body mass index, previous diabetes, C-reactive protein, lactate, procalcitonin, serum creatinine, mean arterial pressure, APACHE II, ultrafiltration between CRRT), only lactate levels on admission (p = 0.002; 95%CI 1.08-1.38) were significant predictor of survival. Conclusion The use of hemoperfusion with Cytosorb in ICU patients with AKI did not reduce 30-day mortality. Patients with prior heart failure had a worse outcome. Serum lactate levels at ICU admission were an independent highly prognostic factor for death within 30 days of admission.

#5627 SYSTEMATIC HISTOLOGICAL SCORING OF TUBULOINTERSTITIAL LESIONS CORRELATE WITH CLINICAL PARAMETERS IN ANCA-ASSOCIATED GLOMERULONEPHRITIS

Abstract Background and Aims Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a small vessel vasculitis affecting multiple organ systems, including the kidney. Small vessels in the kidney include small-sized arteries (interlobular artery, afferent and efferent arteriole), capillaries (glomerular and peritubular capillary) and venules. Although crescentic ANCA glomerulonephritis (GN) is a common histological finding reflecting glomerular small vessel vasculitis, it is reasonable that manifestation of AAV could also contribute to interstitial small vessel vasculitis. Therefore, we here aimed to expand our current knowledge focusing on interstitial vasculitis in ANCA GN by systematic histological scoring of vascular lesions analogous to Banff. Method A total number of 49 kidney biopsies with confirmed renal involvement of AAV at the University Medical Center Göttingen were retrospectively included between 2015 till 2020. A renal pathologist evaluated all biopsies and was blinded to clinical data collection and analysis. A detailed methological section is provided in the Supplementary material and methods section. Results Since previous studies established that crescentic ANCA GN associates with severe kidney injury and acute deterioration of kidney function in AAV, we first systematically scored interstitial vasculitis in association with requirement of renal replacement therapy (RRT). Among all active and chronic tubulointerstitial lesions analogous to the Banff scoring system, the only association between severe kidney injury requiring RRT was observed for interstitial vasculitis in AAV reflected by peritubular capillaritis (ptc, p = 0.0002) and arteritis (v, p = 0.0069), affecting 5/49 (10.2%) and 11/49 (22.4%) of renal biopsies, respectively. Since it is known that severe deterioration of kidney function also correlates with crescentic ANCA GN, we next directly compared glomerular and tubulointerstitial lesions. The fraction of normal glomeruli was inversely associated with interstitial fibrosis (ci), total (ti) and inflammation in IFTA (i-IFTA), whereas glomerular crescents were associated with interstitial inflammation (i), tubulitis (t) and total inflammation (ti). In contrast, global glomerular sclerosis associated with less interstitial inflammation (i) but correlated with interstitial fibrosis (ci) and tubular atrophy (ct), confirming established mechansim that chronic glomerular injury leads to tubular atrophy and interstitial fibrosis. Interestingly, no association between interstitial vasculitis (ptc and v correlating with severe kidney injury) and any glomerular lesion in ANCA GN (also correlating with severe kidney injury) was observed, thereby confirming that interstitial vasculitis contributes to severe kidney injury independent of ANCA GN. By contrast, short-term renal recovery from RRT was equal in both groups, suggesting a distinct association with acute decline of kidney function at disease onset. Conclusion Taken together, by using the Banff scoring system we here expand our current knowledge of renal interstitial lesions in AAV revealing peritubular capillaritis and arteritis as important histological alterations associated with severe kidney injury in a considerable subset of AAV. Furthermore, our findings that interstitial vasculitis did not correlate with crescentic ANCA GN implicate that the characteristics of each vasculitis manifestation are independent and could further improve our understanding of mechanisms contributing to renal injury. These observations suggest that interstitial vasculitis in AAV may also affect long-term prognosis requiring further investigation.

#6573 ASSOCIATION BETWEEN SERUM TOTAL PROTEIN-TO-ALBUMIN RATIO AND PROGNOSIS IN SEPTIC ACUTE KIDNEY INJURY PATIENTS

Abstract Background and Aims Sepsis is the leading cause of acute kidney injury (AKI). Increasing evidence shows that serum total protein-to-albumin ratio (TAR) could serve as inflammation- and nutrition-based prognostic score. The purpose of this study was to assess the effect of TAR on predicting the clinical outcomes of septic AKI patients. Method A retrospective study between August 2015 and August 2021 was performed at West China Hospital of Sichuan University. The primary outcomes were 30-day and 90-day all-cause mortality of septic AKI patients. The secondary outcomes were septic shock, transfer to the intensive care unit, mechanical ventilation, requirement for renal replacement therapy, and stage 3 AKI. Results A total of 309 eligible patients with a median age of 58 years were enrolled. Among the patients, 70.2% were males. In multivariate analysis, after adjustments for age, sex, and other confounding factors, higher baseline TAR was associated with an increased risk of 30-day and 90-day all-cause mortality in septic AKI patients (HR 1.91, 95% CI 1.18–3.09, P = 0.008; HR 1.54, 95% CI 1.01-2.34, P = 0.043, respectively). Subgroup analysis revealed no significant interactions in most strata. We found no relationship between TAR and secondary outcomes. The Youden index of TAR was larger than total protein or albumin alone in predicting both 30-day and 90-day all-cause mortality. Conclusion Increased TAR is an independent predictor for 30-day and 90-day all-cause mortality in septic AKI patients. The predictive performance of TAR outperformed those of total protein and albumin. Further research is needed to corroborate our findings in other cohorts and to compare the predictive ability of baseline TAR and the change in TAR under treatments.

#3285 EXTRACORPOREAL BLOOD PURIFICATION DURING OPEN HEART SURGERY WITH PROLONGED CPB: CYTOSORB 300 VS JAFRON HA330

Abstract Background and Aims Cardiac surgery is maintained by various complications. Major contribution associated with cardiopulmonary bypass (CBP). Cardiac surgery with CPB provokes activation of the cascade mechanism of inflammation with releasing of cytokines and a systemic inflammatory response syndrome (SIRS). Activation of the contact system due to exposure of artificial surface of the bypass circuit to blood cells, endotoxemia, ischemia and reperfusion injury and surgical trauma are all potential triggers of inflammation following CPB. This inflammatory reaction may leads to the development of postoperative complications, including vasoplegia, cytokine storm, myocardial dysfunction, respiratory failure, acute kidney injury, coagulopathy bleeding, and multiple organ dysfunction syndrome (MODS). A number of different strategies, including new pharmacologic agents, CPB circuits and components, and surgical techniques, have been employed during the last few years in attempts to minimize the impact of SIRS on the outcome of cardiac surgical patients. However, the complex pathophysiology of this problem has not allowed, until now, the use of a single strategy. The aim of our study is assessment of early application of extracorporeal cytokine adsorbers to the inflammation system during open-heart surgery with prolonged cardiopulmonary bypass. Method This prospective randomized single-center controlled trial observed patients, who were assigned a planned open cardiac surgery with a duration of cardiopulmonary bypass (CPB) more than 120 minutes between January 2021 to January 2023. Patients were randomized into three groups: CytoSorb -300 group, HA 330 group and the control group. A simple 1:1:1 randomization method was applied. Cytokine hemadsorption was conducted intraoperatively. Two types of cytokine cartridges were applied CytoSorb 300 (Cytosorbents Europe GmbH). НА330 (Jafron Biomedical Co., Ltd. China). The inclusion criteria: age ≥18 years, informed consent to participate in the study, CPB more than 120 min. The exclusion criteria: Age less than 18 years; refusal to participate in the study. Results The data of the HA 330 (n = 22) and CytoSorb300 (n = 22) groups were compared with the data of the control group (n = 22). The primary results and details of the work are given in Tables 1-3. Conclusion Intraoperative hemadsorption may be beneficial for patients who underwent open-heart surgery with prolonged CPB. The early hemadsorption has positive impact to postoperative period after cardiac surgery and may reduce requirement of renal replacement therapy.

#5879 PILOT MONITORING STUDY IN PATIENTS WITH DIABETIC KIDNEY DISEASE USING NORA APPLICATION

Abstract Background and Aims Diabetic Kidney Disease (DKD) is the most common cause of end-stage chronic kidney disease (CKD), conditioning these patients to a worse renal prognosis and higher cardiovascular mortality and/or requirement for renal replacement therapy. The use of novel information and communication technologies (ICTs) focused on the field of health, may facilitates a better quality of life and disease control in these patients. Our objective is to evaluate the effect of monitoring DKD patients using NORA-app. Method Prospective feasibility/validation study of NORA-app in patients with DKD stage G3bA3 or higher, followed in outpatient clinics of a tertiary care hospital. NORA-app is an application for smartphones designed to control risk factors, share educational medical information, communicate via chat with health professionals, increase treatment compliance (Morisky-Green), and collect patient reported outcomes such as anxiety and depression using HADs scale. Clinical-laboratory variables were collected at 3 months and compared to control patients who declined using NORA-app. Results From 01/01/2021 to 03/03/2022 the use of NORA-app was offered to 118 patients, 82 accepted and 36 declined (controls). After a mean follow-up period of 6,04 months and at the time of data extraction 71(86.6%) NORA-app patients remain active users, 2 have completed the follow-up at one year and 9 are inactive (3 due to death and 6 due to non-locatable). There were no differences in baseline characteristics including Creatinine [2.1 (1.6-2.4) vs. 1.9 (1.5-2.5)] mg/dL and alb/creat [962 (475-1784) vs. 1036 (560-2183)] mg/gr between Nora and control patients respectively. The therapeutic compliance rate in the NORA-app group was 77%, improving at 90 days to 91%. Patients in the NORA-group showed significantly lower levels of alb/creat than controls (768(411-1971) mg/g Vs 2039 (974-3214) p = 0.047) at 90-day follow-up. Conclusions In patients with DKD the use of NORA-app was maintained in the long-term, leading to high levels of treatment compliance, and achieving a better disease control. Our study suggests that the generalized use of ICTs may help in the personalized monitoring of these patients to delay the progression of kidney disease.

#5816 RAVULIZUMAB “DE NOVO” IN PEDIATRIC PATIENTS WITH ATYPICAL HEMOLITIC UREMIC SYNDROME: FIRST WORLDWIDE CASES

Abstract Background and Aims Ravulizumab is a long-acting C5 inhibitor that has recently demonstrated its effectiveness in adult and pediatric patients for the control of hemolytic uremic syndrome compared to eculizumab, allowing average annual infusion times of up to 70% less. There is still little evidence in the literature of naïve treatment with this drug in pediatrics. Method We present the first two pediatric cases worldwide with the use of de novo Ravulizumab: the first one in the onset of the disease and the second one, post-kidney transplant Results 13-year-old girl referred from another country with 1 week history of acute gastroenteritis with bloody stools, vomiting and compromise of consciousness. Deterioration of general condition, with laboratory tests compatible with thrombotic microangiopathy (TMA), evolves to anuria and convulsive episode requiring invasive mechanical ventilation, corticosteroid boluses, 6 plasmapheresis sessions and 4 intermittent hemodialysis. One Eculizumab dose (600 mg) was administered in the center of origin and STEC was isolated. At admission presented compromised renal function (AKI III), hemolytic anemia, thrombocytopenia, normal ADAMTS-13, negative direct Coombs and decreased complement. Brain MRI study shows images compatible with multiple foci of necrosis. Due to the persistent requirement of renal replacement therapy and persistent TMA, Ravulizumab was started with a loading dose (2400 mg) and a second dose after 2 weeks. The need for renal replacement therapy ceased with improvement of hemolysis and renal function. Genetic study showed mutation of uncertain significance in heterozygosis in exon 6 (c.881_883, p.Ala292del) with risk polymorphism for HUSa (deletion CFHR3-CFHR1) Case 2: 7-year-old girl (stage 5 CKD) in chronic hemodialysis 3 times/week secondary to aHUS (CD46 mutation) was admitted for kidney transplant from a living donor (father), performing hemodialysis session before surgical intervention. Low-intermediate immunological risk (PRA 0%, 9 HLA matches) and high CMV infectious risk (valganciclovir prophylaxis). Induction treatment: Basiliximab, tacrolimus, mycophenolate and steroids. First dose of Ravulizumab was infused the day before transplantation (900mg), well tolerated. 36 hours after presented acute pulmonary edema as well as a drop in hemoglobin (4g/dL). With normal laboratory hemolysis parameters, urgent abdominal-pelvic CT was performed due to suspicion of bleeding, confirming an active bleeding. Surgical reintervention was decided due to ureteral bleeding and the tunnel was redone with good results. The patient has had a favorable evolution of renal function, with a normal value of creatinine at discharge (0.43 mg/dl). Protein/Creatinine urine ratio (iPr/Cr) increases to a maximum of 8 mg/mg. Negative DSA levels but the option of renal biopsy was assessed and ruled out due to a decrease in proteinuria (iPr/Cr 0.51 mg/mg). She received second dose of ravulizumab after 2 weeks, remain stable with no data on recurrence of her underlying disease today. Conclusión: In the two patients, the initial treatment with Ravulizumab was satisfactory, both in the acute phase of the disease and in the immediate post-transplantation. In the first case we observed a functional recovery from the first dose with no notable adverse effects up today, as in the post-transplant patient, maintaining a good control of TMA despite more spaced dosing (8 weeks). The inclusion of this drug in the therapeutic arsenal opens a new safe treatment route in pediatric patients with HUSa

#4074 FRACTIONATED PLASMA SEPARATION AND ADSORPTION INTEGRATED WITH CONTINUOUS VENO-VENOUS HEMOFILTRATION IN PATIENTS WITH ACUTE LIVER FAILURE

Abstract Background and Aims To observe the clinical efficacy and safety of fractionated plasma separation and adsorption integrated with continuous veno-venous hemofiltration (FPSA-CVVH) treatment in patients with acute liver failure (ALF). Method In this retrospective study, we enrolled patients with ALF (serum total bilirubin&amp;gt;10mg/dl or Model for End-Stage Liver Disease (MELD) Score&amp;gt;18) hospitalized from 2017 to 2022.All patients received the treatment of FPSA-CVVH.The primary measure of treatment efficacy was the reduction ratios (RRs) of bilirubin after each session of FPSA-CVVH. Results 8 patients (68 males and 10 females) with ALF were enrolled. 66 patients (84.6%) exhibited acute kidney injury and required renal replacement therapy (RRT). The score of MELD at baseline was 22.9±7.5. The concentration of serum total bilirubin was 22.05±5.94mg/dL, direct bilirubin was 16.33±4.60mg/dL and indirect bilirubin was 3.43±1.60mg/dL.187 sessions of FPSA-CVVH treatment with 8 hours each were performed. After a single session, serum total bilirubin, direct bilirubin and indirect bilirubin were significantly decreased. RRs was 52.0±7.6% for total bilirubin, 59.4±13.0% for direct bilirubin and 36.9±15.4% for indirect bilirubin. 2 patients changed the filters due to blood coagulation. And other 2 patients exhibited bleeding, including gastrointestinal bleeding and Oozing bleeding. 29 patients (37.2%) survived in discharging from hospital, 12 patients recovered with their liver function, and the remaining 17 patients still needed intermittent artificial liver support therapy. Conclusion FPSA-CVVH therapy was a novol and effective artificial liver support therapy in patients with ALF. It may be considered as a “bridge technique” to the recovery of liver function in critical ill patients with ALF.

#3232 ANTICOAGULANT RELATED NEPHROPATHY – AN UNDERDIAGNOSED COMPLICATION

Abstract Background and Aims Anticoagulant-related nephropathy (ARN) is an underdiagnosed complication of anticoagulant therapy (AT). Method We report 3 cases of ARN. Patient 1: 31 year-old male (M), kidney transplanted for reflux nephropathy, with normal renal function (Rfx) and urinalysis (U), on therapy with tacrolimus (FK), everolimus and mycophenolate. He started edoxaban (E) (60 mg od) for deep vein thrombosis (DVT). After 10 days he developed hematuria and Acute Kidney Injury (AKI). Ruled out urological and infectious causes, we performed kidney biopsy (KB) which showed extensive tubular necrosis (TN), erythrocyte casts (cRBC) and glomerular hemorrhage (EG). Perl's stain (PS) showed iron deposits in tubular cells released by erythrocytes lysis (Fig. 1). Although E posology was adequate the concomitant intake of FK by reducing CYP3A4 metabolism of E resulted in over anticoagulation (OAC), demonstrated by the dosage of the factor Xa (FXa) at peak. Upon withdrawal of AT, Rfx and U normalized. Patient 2: 73-year-old M with hypertension and mild chronic kidney disease (CKD) on antiplatelet therapy (ASA 100 mg od) for biological valve prosthesis and AT with Enoxaparin sodium (Es) (4000UI od) for DVT prophylaxis. He was admitted to the hospital for fever and hypotensive episodes. Microbiological, neoplastic and immune investigations were negative. A progressive worsening of Rfx associated with macro-hematuria was observed, requiring renal replacement therapy (RRT). KB showed a post-infectious glomerulonephirits, but in the hypothesis that tubular damage was enhanced by antiplatelet/AT, PS was performed and resulted positive. OAC was confirmed by the dosage of the factor Xa (FXa) at peak. After withdrawal of therapy, progressive improvement of the Rfx and hematuria were observed, such as to allow the suspension of the RRT. Patient 3: 54 year-old M with kidney and lung involvement of ANCA-associated vasculitis. After rituximab induction therapy he showed marked improvement on lung and renal function and antibody titer (c-ANCA PR3 positive). He experienced an unusual worsening of Rfx and hematuria after starting a AT (Es 6000 UI BID) to treat a DVT. A KB was performed in the suspicion of ARN. The histology revealed an extensive TN, numerous cRBC with extracapillary glomerulonephritis and PS positive. IF was negative. OAC was confirmed and adjustment of anticoagulation dose for glomerular filtration rate resulted in improvement of Rfx. Results ARN is a not uncommon occurrence in cases of OAC and glomerular fragility (Table 1). Conclusion ARN should be suspected in predisposed patients in whom glomerular hyperfiltration or preexisting GN during OAC facilitate EG. Attention should be given to drug interactions that can induce an unrecognized OAC. The cases described underline the need for careful monitoring of U, RFx and FXa activity to promptly treat this complication, avoiding permanent damage.

#6242 CLINICAL CHARACTERISTICS OF HEMODIALYSIS PATIENTS FROM AFRICAN COUNTRIES OF PORTUGUESE OFFICIAL LANGUAGE: A PORTUGUESE COHORT

Abstract Background and Aims Chronic kidney disease (CKD) is a leading cause of morbidity and mortality worldwide, with African descendants being at increased risk of occurrence and progression to end-stage renal disease (ESRD). However, the burden of CKD and ESRD in African continent is still largely conjectural and access to treatment of CKD is restricted in those countries. Africa contributes to &amp;lt;10% of the total renal replacement therapy (RRT) patients worldwide, mainly due to the high costs associated. The purpose of this analysis was to describe the clinical characteristics and outcomes of patients from African Countries of Portuguese Official Language (ACPOL) who integrated the HD program of a tertiary hospital in Portugal. Method Retrospective analysis of 126 African patients who integrated the HD program of a tertiary hospital in Portugal, between January 2015 and December 2019. Last follow-up was ascertained in January 2021. Results Mean age was 49.9 ± 14.1 years, and 53.6% were male (n = 71). Hypertension was a comorbidity in 96.0% (n = 121). Twenty-one patients came from Angola (16.7%), 53 from Cape Verde (42.1%), 23 from Guinea-Bissau (18.3%), 20 from Saint Thomas and Prince (15.9%), and 9 from Mozambique (7.1%). Motive for referral to Portugal was RRT requirement in 93.7% of the cases (n = 118) and vascular access (VA) dysfunction in 6.3% (n = 8); these 8 patients with VA dysfunction were already on hemodialysis program before their evacuation to Portugal and they were mainly from Cape Verde (n = 4), Angola (n = 3), and one patient from Guinea-Bissau. At arrival, patients who initiated HD in our unit had mean serum creatinine 9.4 ± 4.4 mg/dL, urea 182.5 ± 109.1 mg/dL, Hb 9.6 ± 1.7 g/dL, serum albumin 3.6 ± 0.6 g/dL, PTH 491.7 ± 392.6 pg/mL. Patients referred due to VA dysfunction had mean Hb 10.1 ± 1.8 g/dL, serum albumin 3.7 ± 1.0 g/dL, PTH 918.9 ± 541.6 pg/mL. There were no statistically significant differences in both groups concerning country of origin, although hypoalbuminemia was more frequent in patients from Saint Thomas and Prince (50%) and Angola (42.9%). All patients started HD with a central venous catheter (CVC). During follow-up, CVC remained the vascular access in 51.6% (n = 65), arteriovenous fistula in 42.9% (n = 54), and arteriovenous graft in 5.6% patients (n = 7). Nine patients had exhaustion of VA for HD. Mean follow-up time was 70.5 ± 41.3 months, 1.6% of the patients transitioned to peritoneal dialysis (n = 2) and 15.1% were submitted to renal transplantation (n = 18). The mortality rate during follow-up was 14.3% (n = 18). Conclusion There are few studies about African patients undergoing HD and this is the first study presenting the clinical characteristics and outcomes of hemodialysis patients from ACPOL. These are young patients, almost all with hypertension, with a high prevalence of anemia, malnutrition, and secondary hyperparathyroidism. All patients started HD with CVC and several presented multiple access dysfunction. These data reinforce the urgent need of improvement and investment in African countries’ healthcare, especially on what concerns the ESRD, as it contributes to serious consequences in these patients’ survival and quality of life. With the cooperation protocol, Portugal provides these patients with RRT, treatment of the CKD complications, VA care, possibility of peritoneal dialysis and renal transplantation, ultimately improving their chance of survival and quality of life.

#6863 MANAGEMENT AND OUTCOMES OF SEPSIS ASSOCIATED ACUTE KIDNEY INJURY IN CRITICALLY ILL PATIENTS

Abstract Background and Aims Sepsis-associated acute kidney injury (AKI) remains a major cause of mortality in patients with critical illness and has an especially high health-related burden in developing countries. However, only a few clinical studies have focused on the clinical characteristics and prognosis of septic AKI, especially in low-income settings. Therefore, the aim of our study was to describe the clinical profile, management and outcome of critically ill patients with sepsis associated AKI. Methods A retrospective observational study of critically ill patients with septic AKI was performed from March 2020 to June 2021 at our university hospital. Sepsis was diagnosed clinically by the presence of acute infection and new organ dysfunction. The presence of AKI was evaluated using the Acute Kidney Injury Network (AKIN) criteria. Patients with preexisting ESRD and those who did not fulfill at least one predefined criterion for AKI were excluded. Results A total of 105 patients with a median age of 58.9 years (31-78) were enrolled, including 69 and 36 patients with persistent and transient AKI, respectively. The mean SAPS II score was 51.8 (38-77). The primary source of sepsis was mainly abdominal (42.8%). AKI was defined by oliguria in 18 patients (17.1%), by creatinine elevation in 65 patients (61.9%), and by both criteria in 22 patients (21%). Septic AKI was associated with great aberrations in hemodynamics, with 71 patients (67.6%) requiring vasoactive therapy and 65 patients (61.9%) requiring mechanical ventilation. AKI severity according to the AKIN classification scheme was determined to be stage 1 in 32 patients (30.5%), stage 2 in 22 patients (20.9%), and stage 3 in 51 patients (48.6%). Overall, 75.2% of the cohort required renal replacement therapy (RRT). Hospital survival was 63.8% (n = 23) in patients with transient AKI and 43.5% (n = 30) in patients with persistent AKI. Conclusion Sepsis is the main cause of AKI in intensive care units, accounting for up to 50% of cases. Our results suggest that septic AKI is associated with higher disease severity scores at admission, requirement of vasoactive drugs, need for mechanical ventilation and increased hospital mortality. Further studies are required, especially in developping countries, to implement more preventive measures and therapeutic interventions to decrease CKD progression and mortality in these patients.

#4731 THE CHANGING HAEMODIALYSIS POPULATION IN A SINGLE UK CENTRE: A POST PANDEMIC PHENOMENON?

Abstract Background and Aims Following the Covid-19 pandemic, UK dialysis centres have seen a sharp increase in numbers of patients requiring renal replacement therapy (RRT) particularly haemodialysis (HD). This has resulted in pressures on dialysis capacity and staffing. There may also have been negative effects on other aspects of quality of care, such as a fall in the proportion of patients dialysing via an Arterio-venous fistula (AVF) or worsening anaemia. To study this further, we conducted a retrospective observational study to describe the incident and prevalent HD populations in the post-Covid pandemic period and compare these against pre-pandemic patterns, in a single UK dialysis centre. Method We reviewed data on prevalent HD patient numbers across our service. We specifically collected data from all patients commencing HD between January 2021 and December 2022 using electronic medical records. We collected information on time known to renal prior to starting dialysis, clinic data including which types of clinic attended, documentation of pre-dialysis decisions about modality as well as vascular access referrals, vascular access clinics and vascular access surgery as well as haemoglobin (Hb) at first dialysis. We compared figures with published pre-pandemic data from the 23rd annual UK Renal Registry report on data collected to December 2019 for our centre. We defined a planned start to dialysis as patients who were known to renal &amp;gt;90 days. This aligns with the registry definition. We compared proportional data using the chi square test. Results Comparing prevalent data in Dec. 2022 with Dec 2019, there was a 17% increase in the prevalent HD population from 298 to 349. The proportion of patients dialysing via an AVF fell from 88% to 80% (p = 0.006). The spread across different types of HD in Dec.2022 remained static at 71% In-Centre HD (72% in Dec 2019), 11% Satellite HD (9% in 2019) and 17% HHD (18% 2019) with overall numbers rising across all HD modalities (p for trend = 0.37). PD numbers also rose from 58 to 71 keeping the total percentage on home therapies stable at 31% in our unit. From Jan. 2021- Dec. 2022 inclusive 147 people commenced HD of whom 115 (78%) had planned starts. This compares to 58 starting HD in 2019 and 79% planned (p = 0.85). There was a significant fall in the proportion of planned start HD patients who commenced dialysis with an AVF/AVG, from 81% in 2019 to 56% in 2021-22 (p = 0.003). Themes emerged n planned starters who did not start HD with an AVF/AVG and are detailed in Figure 1. Median Hb level of planned starts on HD was lower at only 94 for 2021-22 and 99 in 2019. Looking in detail at those missing appointments in clinics, 33% had prior documented evidence of fear of Covid-19. Delays in AVF surgery consisted of delayed and cancelled theatre dates, failed AVF requiring re-do or AVF awaiting further intervention at time of dialysis initiation. In the group with a last minute change in decision sighted reasons included: worsening eyesight, development of dementia in partner, reducing mobility. Others changed their mind after further input from the PD team. Despite attending the Advanced Kidney Clinic (AKC) there were still a number of patients with no decision at all. Cancellation of group sessions for dialysis education persisted in our centre until mid-2022 and may have contributed to reduced timely decision making as well as late modality switches. All those with an early failure of PD (defined as &amp;lt; 90 days) had chosen PD prior to the Covid-19 pandemic with intervening remote visits in AKC. Conclusion Following the Covid-19 pandemic, unexpected and unprecedented changes in the HD incident population have been observed, resulting in pressures on dialysis services. In particular, we report an increase in absolute number of dialysis patients, a significant fall in the proportion of patients initiating dialysis with definitive vascular access and a rise in those starting anaemic. This was not related to a change in the proportion of patients with planned starts but may be related to delayed shared decision making as a result of remote consultations and greater delays in vascular access surgery. We have identified a number of areas for service improvement.

#3312 EFFICACY OF TRANSCATHETER AORTIC VALVE IMPLANTATION FOR SEVERE AORTIC VALVE STENOSIS IN HEMODIALYSIS PATIENTS

Abstract Background and Aims In Japan, of the &amp;gt;340,000 chronic dialysis patients, approximately 60% have lifestyle-related diseases including diabetes and nephrosclerosis. Two-thirds of maintenance dialysis patients (age, ≥65 years) often develop aortic stenosis (AS) and other serious and complex systemic cardiovascular disease complications associated with chronic kidney disease mineral and bone disorder (CKD-MBD). Furthermore, renal function loss and a prolonged state of renal failure are observed requiring renal replacement therapy (RRT). AS in dialysis patients progresses quickly, and the frequency of hospitalized treatment for heart failure increases with the worsening condition, leading to ADL deterioration, which may subsequently cause dialysis hypotension/interruption. At our hospital, of the 420 maintenance dialysis patients who died during hospitalization in 5 years before 2020 (420/2,637 = 16%), 32 cases (8%) developed AS complications, which became their direct cause of death in 12 cases (3%), and aortic valve replacement (AVR) was performed in 5 cases (1%). Maintenance hemodialysis patients (HD) are at high risk group and have a poor prognosis for life. Previously, transcatheter aortic valve implantation (TAVI) was not indicated., but recently TAVI has been approved in Japan. Efficacy of TAVI for HD patients remains unclear, here we investigated several outcomes. Method A total of 123 maintenance dialysis patients with severe AS were included in 2019–2021. We examined TAVI group and AVR group for length of hospital stay, hospitalization costs, life expectancy, and rates of complications such as occurrence of arrhythmias. Results Over a 3-year period, we performed TAVI for 58 maintenance dialysis patients (mean age, 81 years); their median duration of hospitalization was 14 days for a median cost of 6,259,350 JPY. The mean age was older than that of 66 patients who underwent open-heart AVR during the same period (mean age, 73 years; 35 days for 7,192,570 JPY); therefore, the cost was less, and the rate of complications, including vital prognosis and arrhythmia, was not inferior in hospitalization period. Conclusion In conclusion, TAVI is effective for elderly maintenance dialysis patients with severe AS and has a positive health care economics, ADL maintenance.